Association analysis of a functional variant in ATXN2 with schizophrenia

Fuquan Zhang, Guoqiang Wang, Yin Yao Shugart, Yong Xu, Chenxing Liu, Lifang Wang, Tianlan Lu, Hao Yan, Yanyan Ruan, Zaohuo Cheng, Lin Tian, Chunhui Jin, Janmin Yuan, Zhiqiang Wang, Wei Zhu, Leiming Cao, Yansong Liu, Weihua Yue, Dai Zhang

Research output: Contribution to journalArticle

Abstract

Schizophrenia (SZ) is a severe mental disorder characterized by multiple neurodevelopmental dysfunctions including a breakdown of thinking process and a deficit of typical emotional responses. Ataxin-2 (ATXN2) plays vital roles in cell proliferation and growth, and functional mutations of ATXN2 cause neurodegenerative phenotypes, including spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS). To explore the possible role of ATXN2 in SZ, we conducted a two-stage study to examine the association of ATXN2 polymorphisms with SZ in the Han Chinese population. Association analysis of seven SNPs in 768 patients and 1348 controls revealed two associated SNPs, including rs630511 (P= 1.76E-4) and rs7969300 (P= 5.08E-4). We examined these two SNPs in a validation sample of 1957 patients and 1509 controls, and observed an association of rs7969300 with SZ (P= 5.03E-3). The SNP rs7969300 is a non-synonymous SNP causing a Ser to Asn substitution, which is predicted to increase the protein stability of ATXN2. Our data suggest that the ATXN2 gene may confer vulnerability for SZ, adding further evidence for the genetic variants within the developmental pathway in the illness.

Original languageEnglish (US)
Pages (from-to)24-27
Number of pages4
JournalNeuroscience Letters
Volume562
DOIs
StatePublished - Mar 6 2014
Externally publishedYes

Fingerprint

Schizophrenia
Single Nucleotide Polymorphism
Spinocerebellar Ataxias
Protein Stability
Amyotrophic Lateral Sclerosis
Mental Disorders
Ataxin-2
Cell Proliferation
Phenotype
Mutation
Growth
Population
Genes

Keywords

  • ATXN2
  • Rs7969300
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Zhang, F., Wang, G., Shugart, Y. Y., Xu, Y., Liu, C., Wang, L., ... Zhang, D. (2014). Association analysis of a functional variant in ATXN2 with schizophrenia. Neuroscience Letters, 562, 24-27. https://doi.org/10.1016/j.neulet.2013.12.001

Association analysis of a functional variant in ATXN2 with schizophrenia. / Zhang, Fuquan; Wang, Guoqiang; Shugart, Yin Yao; Xu, Yong; Liu, Chenxing; Wang, Lifang; Lu, Tianlan; Yan, Hao; Ruan, Yanyan; Cheng, Zaohuo; Tian, Lin; Jin, Chunhui; Yuan, Janmin; Wang, Zhiqiang; Zhu, Wei; Cao, Leiming; Liu, Yansong; Yue, Weihua; Zhang, Dai.

In: Neuroscience Letters, Vol. 562, 06.03.2014, p. 24-27.

Research output: Contribution to journalArticle

Zhang, F, Wang, G, Shugart, YY, Xu, Y, Liu, C, Wang, L, Lu, T, Yan, H, Ruan, Y, Cheng, Z, Tian, L, Jin, C, Yuan, J, Wang, Z, Zhu, W, Cao, L, Liu, Y, Yue, W & Zhang, D 2014, 'Association analysis of a functional variant in ATXN2 with schizophrenia', Neuroscience Letters, vol. 562, pp. 24-27. https://doi.org/10.1016/j.neulet.2013.12.001
Zhang, Fuquan ; Wang, Guoqiang ; Shugart, Yin Yao ; Xu, Yong ; Liu, Chenxing ; Wang, Lifang ; Lu, Tianlan ; Yan, Hao ; Ruan, Yanyan ; Cheng, Zaohuo ; Tian, Lin ; Jin, Chunhui ; Yuan, Janmin ; Wang, Zhiqiang ; Zhu, Wei ; Cao, Leiming ; Liu, Yansong ; Yue, Weihua ; Zhang, Dai. / Association analysis of a functional variant in ATXN2 with schizophrenia. In: Neuroscience Letters. 2014 ; Vol. 562. pp. 24-27.
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abstract = "Schizophrenia (SZ) is a severe mental disorder characterized by multiple neurodevelopmental dysfunctions including a breakdown of thinking process and a deficit of typical emotional responses. Ataxin-2 (ATXN2) plays vital roles in cell proliferation and growth, and functional mutations of ATXN2 cause neurodegenerative phenotypes, including spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS). To explore the possible role of ATXN2 in SZ, we conducted a two-stage study to examine the association of ATXN2 polymorphisms with SZ in the Han Chinese population. Association analysis of seven SNPs in 768 patients and 1348 controls revealed two associated SNPs, including rs630511 (P= 1.76E-4) and rs7969300 (P= 5.08E-4). We examined these two SNPs in a validation sample of 1957 patients and 1509 controls, and observed an association of rs7969300 with SZ (P= 5.03E-3). The SNP rs7969300 is a non-synonymous SNP causing a Ser to Asn substitution, which is predicted to increase the protein stability of ATXN2. Our data suggest that the ATXN2 gene may confer vulnerability for SZ, adding further evidence for the genetic variants within the developmental pathway in the illness.",
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AU - Wang, Guoqiang

AU - Shugart, Yin Yao

AU - Xu, Yong

AU - Liu, Chenxing

AU - Wang, Lifang

AU - Lu, Tianlan

AU - Yan, Hao

AU - Ruan, Yanyan

AU - Cheng, Zaohuo

AU - Tian, Lin

AU - Jin, Chunhui

AU - Yuan, Janmin

AU - Wang, Zhiqiang

AU - Zhu, Wei

AU - Cao, Leiming

AU - Liu, Yansong

AU - Yue, Weihua

AU - Zhang, Dai

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N2 - Schizophrenia (SZ) is a severe mental disorder characterized by multiple neurodevelopmental dysfunctions including a breakdown of thinking process and a deficit of typical emotional responses. Ataxin-2 (ATXN2) plays vital roles in cell proliferation and growth, and functional mutations of ATXN2 cause neurodegenerative phenotypes, including spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS). To explore the possible role of ATXN2 in SZ, we conducted a two-stage study to examine the association of ATXN2 polymorphisms with SZ in the Han Chinese population. Association analysis of seven SNPs in 768 patients and 1348 controls revealed two associated SNPs, including rs630511 (P= 1.76E-4) and rs7969300 (P= 5.08E-4). We examined these two SNPs in a validation sample of 1957 patients and 1509 controls, and observed an association of rs7969300 with SZ (P= 5.03E-3). The SNP rs7969300 is a non-synonymous SNP causing a Ser to Asn substitution, which is predicted to increase the protein stability of ATXN2. Our data suggest that the ATXN2 gene may confer vulnerability for SZ, adding further evidence for the genetic variants within the developmental pathway in the illness.

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